Centre Investigation Clinique Inserm CIC 0802, CHU de Poitiers, Poitiers, France.
Curr Opin Hematol. 2012 Mar;19(2):102-9. doi: 10.1097/MOH.0b013e32834ff610.
Imatinib was registered several years ago for the treatment of chronic-phase chronic myeloid leukemia. Because of the occurrence of resistance with imatinib, new drugs have been developed recently, two of which, nilotinib and dasatinib, are being registered for frontline therapy. However physicians may be confused as to how to treat and manage their newly diagnosed patients. The value of new scoring systems and well known surrogate markers such as cytogenetic and molecular responses as well as recent data from phase II or III trials are presented and discussed.
The analysis of trials comparing 400 mg of imatinib to higher doses suggests that 400 mg still seems to be the appropriate initial dose. However, doses of 800 mg could be proposed for high-risk patients or for those with slower response. Sokal and Euro scoring systems are useful and should be calculated before initiating the treatment. The achievement of early complete cytogenetic response is still a valid surrogate marker, although close molecular monitoring is also mandatory. Second-generation tyrosine kinase inhibitors have proved their efficacy by reducing the rate of progression to advanced phases.
Long-term follow-up of ongoing trials investigating tyrosine kinase inhibitors, alone or in combination with interferon, will assess their efficacy on overall survival.
伊马替尼数年前获准用于治疗慢性期慢性髓性白血病。由于伊马替尼耐药的发生,最近开发了新药,其中尼洛替尼和达沙替尼正被注册用于一线治疗。然而,医生可能会困惑于如何治疗和管理新诊断的患者。本文介绍并讨论了新的评分系统和众所周知的替代标志物(细胞遗传学和分子反应)的价值,以及来自 II 期或 III 期试验的最新数据。
比较伊马替尼 400mg 与较高剂量的试验分析表明,400mg 似乎仍然是合适的初始剂量。然而,对于高危患者或反应较慢的患者,可以建议使用 800mg 的剂量。Sokal 和 Euro 评分系统是有用的,应在开始治疗前计算。早期完全细胞遗传学缓解仍然是一个有效的替代标志物,尽管密切的分子监测也是必需的。第二代酪氨酸激酶抑制剂已通过降低进展为晚期阶段的速度证明了其疗效。
正在进行的酪氨酸激酶抑制剂单独或联合干扰素的试验的长期随访将评估其对总生存期的疗效。